PMID- 11606486
OWN - NLM
STAT- MEDLINE
DCOM- 20020115
LR  - 20220331
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 15
IP  - 14
DP  - 2001 Dec
TI  - 1alpha,25-Dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic 
      action.
PG  - 2751-3
AB  - We reported recently that suppression of the renal 1alpha,25-dihyroxyvitamin D3 
      (1lpha,25-(OH)2-D3) production in aP2-agouti transgenic mice by increasing 
      dietary calcium decreases adipocyte intracellular Ca2+ ([Ca2+]i), stimulates 
      lipolysis, inhibits lipogenesis, and reduces adiposity. However, it was not clear 
      whether this modulation of adipocyte metabolism by dietary calcium is a direct 
      effect of inhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i. Accordingly, we have 
      now evaluated the direct role of 1alpha,25-(OH)2-D3. Human adipocytes exhibited a 
      1alpha,25-(OH)2-D3 dose-responsive (1-50 nM) increase in [Ca2+]i (P<0.01). This 
      action was mimicked by 1alpha,25-dihyroxylumisterol3 
      (1alpha,25-(OH)2-lumisterol3) (P<0.001), a specific agonist for a putative 
      membrane vitamin D receptor (mVDR), and completely prevented by 
      1b,25-dihydroxyvitamin D3 (1beta,25-(OH)2-D3), a specific antagonist for the 
      mVDR. Similarly, 1alpha,25-(OH)2-D3 (5 nM) caused 50%-100% increases in adipocyte 
      fatty acid synthase (FAS) expression and activity (P<0.02), a 61% increase in 
      glycerol-3-phosphate dehydrogenase (GPDH) activity (P<0.01), and an 80% 
      inhibition of isoproterenol-stimulated lipolysis (P<0.001), whereas 
      1beta,25-(OH)2-D3 completely blocked all these effects. Notably, 
      1alpha,25-(OH)2-lumisterol3 exerted more potent effects in modulating adipocyte 
      lipid metabolism, with 2.5- to 3.0-fold increases in FAS expression and activity 
      (P<0.001) and a threefold increase in GPDH activity (P<0.001). Also 
      1alpha,25-(OH)2-lumisterol3 was approximately twice as potent in inhibiting basal 
      lipolysis (P<0.025), whereas 1beta,25-(OH)2-D3 completely blocked all these 
      effects. These data suggest that 1alpha,25-(OH)2-D3 modulates adipocyte Ca2+ 
      signaling and, consequently, exerts a coordinated control over lipogenesis and 
      lipolysis. Thus, a direct inhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i may 
      contribute to an anti-obesity effect of dietary calcium, and the mVDR may 
      represent an important target for obesity.
FAU - Shi, H
AU  - Shi H
AD  - University of Tennessee, Knoxville, Tennessee 37996, USA.
FAU - Norman, A W
AU  - Norman AW
FAU - Okamura, W H
AU  - Okamura WH
FAU - Sen, A
AU  - Sen A
FAU - Zemel, M B
AU  - Zemel MB
LA  - eng
PT  - Journal Article
DEP - 20011015
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Dihydroxycholecalciferols)
RN  - 0 (Lipids)
RN  - 0 (RNA, Messenger)
RN  - EC 1.1.- (Glycerolphosphate Dehydrogenase)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - FXC9231JVH (Calcitriol)
RN  - L628TT009W (Isoproterenol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adipocytes/*drug effects/metabolism
MH  - Calcitriol/*pharmacology
MH  - Calcium/metabolism
MH  - Dihydroxycholecalciferols/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fatty Acid Synthases/drug effects/genetics/metabolism
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glycerolphosphate Dehydrogenase/drug effects/metabolism
MH  - Humans
MH  - Isoproterenol/pharmacology
MH  - Lipids/biosynthesis
MH  - Lipolysis/drug effects
MH  - RNA, Messenger/drug effects/genetics/metabolism
EDAT- 2001/10/19 10:00
MHDA- 2002/01/16 10:01
CRDT- 2001/10/19 10:00
PHST- 2001/10/19 10:00 [pubmed]
PHST- 2002/01/16 10:01 [medline]
PHST- 2001/10/19 10:00 [entrez]
AID - 01-0584fje [pii]
AID - 10.1096/fj.01-0584fje [doi]
PST - ppublish
SO  - FASEB J. 2001 Dec;15(14):2751-3. doi: 10.1096/fj.01-0584fje. Epub 2001 Oct 15.